Get access

Time-of-flight SIMS as a novel approach to unlocking the hypoxic properties of cancer

Authors

  • Emily G Armitage,

    1. Doctoral Training Centre for Integrative Systems Biology, School of Chemical Engineering and Analytical Science, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK
    Search for more papers by this author
  • Helen L Kotze,

    1. Doctoral Training Centre for Integrative Systems Biology, School of Chemical Engineering and Analytical Science, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK
    Search for more papers by this author
  • John S Fletcher,

    1. Surface Analysis Research Centre, School of Chemical Engineering and Analytical Science, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK
    Search for more papers by this author
  • Alex Henderson,

    1. Surface Analysis Research Centre, School of Chemical Engineering and Analytical Science, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK
    Search for more papers by this author
  • Kaye J Williams,

    1. School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK
    Search for more papers by this author
  • Nicholas P Lockyer,

    Corresponding author
    • School of Chemistry, University of Manchester, Manchester, UK
    Search for more papers by this author
  • John C Vickerman

    1. Surface Analysis Research Centre, School of Chemical Engineering and Analytical Science, Manchester Interdisciplinary Biocentre, University of Manchester, Manchester, UK
    Search for more papers by this author

Nicholas Lockyer, School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK.

E-mail: Nick.Lockyer@manchester.ac.uk

Abstract

It is known that hypoxia-inducible factor 1 (HIF-1) activity results in the coordinated up-regulation of a large number of proteins that facilitate cell survival in tumours; however, the effect of HIF-1 on cancer metabolism is less well characterised. With knowledge of the specific effect of HIF-1 on cancer metabolism, biomarkers could be identified for which new drugs could be targeted. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) offers the potential to analyse intact cells in situ and has a mass spectral coverage that is applicable to metabolic profiling. It has been used to analyse the effects of HIF-1 on multicellular tumour models. Multicellular tumour spheroids (MTSs) have been cultured from human colon carcinoma cells with and without the expression of HIF-1, and the surface of the cross sections of each MTS has been analysed. Because metabolic profiling is an emerging field in ToF-SIMS, there is a requirement to determine which metabolites can be detected using this technique and which of those can be identified in complex mixtures within biological samples. For this, a selection of metabolites have been analysed, and the ToF-SIMS standard spectra acquired have been used to localise metabolites in MTS sections. The comparison of metabolic profiles of MTSs with and without the expression of HIF-1 has elucidated potential biomarkers for tumour survival in hypoxia, some of which may be HIF-1 regulated. Copyright © 2012 John Wiley & Sons, Ltd.

Get access to the full text of this article

Ancillary